1. Approach to Acute Kidney Injury
Dr. Mohammed Al-Ghonaim MBBS,FRCP(C)
November 2014

2. Objective At the end of this tutorial you will be able to: Define AKI
Know the epidemiology of AKI
Know the etiology of AKI
Manage AKI
Diagnose AKI
Treat AKI

3. Acute Kidney Injury (AKI)
Deterioration of renal function over a period of hours to days, resulting in
the failure of the kidney to excrete nitrogenous waste products and
to maintain fluid and electrolyte homeostasis
Oliguria: <400 ml urine output in 24 hours
Anuria: <100 ml urine output in 24 hours

4. Acute Kidney Injury (definition)
ARF in one study was defined as:
a 0.5 mg/dL increase in serum creatinine if the baseline serum creatinine was ≤1.9 mg/dL,
an 1.0 mg/dL increase in serum creatinine if the baseline serum creatinine was 2.0 to 4.9 mg/dL, and
a 1.5 mg/dL increase in serum creatinine if the baseline serum creatinine was ≥5.0 mg/dl

5. Acute Kidney Injury (AKI)
An abrupt (within 48 hours) absolute increase in increase in creatinine by 0.3 mg/dl ( µmol/l)or percentage increase of >50% from base line or urine output <0.5 ml/hour for 6 hours

6. Acute Kidney Injury Definition:
“Acute kidney injury, mortality, length of stay, and costs in hospitalized patients”
19,982 pts admitted to academic medical centre in SF 9,205 pts with >1 creatinine results
Rise in creatinine
Multivariable OR
(hospital mortality)
≥ 0.3 mg/dl (26.4 μmol/L)
4.1
≥ 0.5 mg/dl (45 μmol/L)
6.5
≥ 1.0 mg/dl (90 μmol/L)
9.7
≥ 2.0 mg/dl (180 μmol/L)
16.4
Chertow et al. JASN 2005; 16:

7. Acute Kidney Injury Stages:
Creatinine criteria
Urine Output
AKI stage I
1.5-2 times baseline OR
0.3 mg/dl increase from baseline
(≥ 26.4 μmol/L)
<0.5 ml/kg/h for >6 h
AKI stage II
2-3 times baseline
<0.5 ml/kg/h for >12 h
AKI stage III
3 times baseline
0.5 mg/dl (44 μmol/L) increase if baseline
> 4mg/dl(≥ 354 μmol/L)
Any renal replacement therapy given
<0.3 ml/kg/h for >24 h
Anuria for >12 h
Mehta R et al. Crit Care 2007;11(2):R31
Ostermann et al. Critical Care :R144

8. Epidemiology It occurs in 5%of all hospitalized patients and
35% of those in intensive care units
Mortality is high:
up to 75–90% in patients with sepsis
35–45% in those without

9. Median hospital length of stay (LOS) stratified by single acute organ system dysfunction (AOSD), including acute renal failure (ARF).

10. Acute Kidney Injury Impact
Correlation between AKI classification and outcome
22,303 adult patients admitted to 22 ICUs in UK and Germany
between 1989–1999 with ICU stay ≥24 hours
No AKI
65.6%
AKI I
19.1%
AKI II
3.8%
AKI III
12.5%
Mean age
60.5
62.1
60.4
61.1
ICU mortality
10.7%
20.1%
25.9%
49.6%
Hospital mortality
16.9%
29.9%
35.8%
57.9%
Length of stay in ICU (median)
2 d
5 d
8 d
9 d
Ostermann et al, Critical Care 2008;12:R144

11. Acute Kidney Injury
Clinical outcome:

12. Etiology of ARF

13. Acute kidney injury Types and consequences:
Pre renal
Renal
Post Renal
Volume depletion
Decreased cardiac output
Acute Tubular necrosis (ATN)
Acute interstitial nephritis (AIN
Acute Glomerulonephritis (GN)
Ureteric obstruction
Bladder neck obstruction
Urethral obstruction
Calcification
Clinical Consequences
Chronic Kidney disease
End Stage Renal Disease
Hospitalization
Mortality

14. Etiology of ARF

15. Pre-renal AKI Volume depletion Decreased cardiac output
Renal losses (diuretics, polyuria)
GI losses (vomiting, diarrhea)
Cutaneous losses (burns, Stevens-Johnson syndrome)
Hemorrhage
Pancreatitis
Decreased cardiac output  
Heart failure
Pulmonary embolus
Acute myocardial infarction
Severe valvular heart disease
Abdominal compartment syndrome (tense ascites)

16. Acute Kidney Injury Scenario 1
75 years old female, known to have:
DM II
HTN
Presented with nausea, vomiting and diarrhea for 3 days
Medication: Insulin, lisinopril,

17. Acute Kidney Injury Scenario 1
Vital Signs
Result
Normal Range
Pulse
95/min
60-100/min
Blood pressure
112/67 mmHg
130/80 mmHg
Temperature
37.0°C °C
Jugular venous pressure was low, dry mucus membrane
Cardiovascular examination:
Normal first and second heart sound no added sound or murmurs.
Respiratory system examination:
Lungs are clear to percussion and auscultation
Abdominal examination:
No tenderness, liver and spleen were not palpable.

18. Acute Kidney Injury Scenario 1
Test
Value
Normal values
Creatinine
154 µmol/L
µmol/L
Urea
23 mmol/L
mmol/L
Potassium
4.3 mmol/L
mmol/L
Sodium
137 mmol/L
mmol/L
Bicarbonate 20
22-26 mmol/l

19. Acute Kidney Injury Acute vs Chronic
History
Short (days-week)
Long (month-years)
Haemoglobin
Normal
Low
Renal size
Reduced
Serum Creatinine
Acute reversible increase
Chronic irreversible

20. Acute Kidney injury Scenario 1
Complete blood count (CBC)
Result
Normal reference ranges
Hemoglobin
134 g/L
Male : g/L ( g/dl )
Female : g/L ( g/dl )
White cell count
12 x 10* 9/L
x 10* 9/L
Platelet count
198 x 10*9/L
x 10* 9/L

21. Acute Kidney Injury Result Normal values Color Dark yellow
Amber yellow
Character
clear PH
6.0 acidic
Specific gravity
1.025
Protein +1
(-)
Glucose
Red blood cells
1-2 /hpf
Hemoglobin
Negative
Pus cells (WBC)
Epithelial cells
Amorphus phosphate
Bacteria
Granular cast

22. Acute Kidney Injury Scenario 1
What is your diagnosis?
Acute Kidney Injury.
What is the etiology of AKI?
Pre renal (dehydration)
What do you expect to fined in urine analysis?
Normal
What do you expect urinary Na, osmolality?
Urinary Na<10
Osmolality > 300
Fractional excretion of Na <1%

23. Post-renal AKI Ureteric obstruction Bladder neck obstruction
Stone disease,
Tumor,
Fibrosis,
Ligation during pelvic surgery
Bladder neck obstruction
Benign prostatic hypertrophy [BPH]
Cancer of the prostate
Neurogenic bladder
Drugs(Tricyclic antidepressants, ganglion blockers,
Bladder tumor,
Stone disease, hemorrhage/clot)
Urethral obstruction (strictures, tumor)

24. Acute Kidney Injury Scenario 2
75 years old Saudi male,
DM II, HTN and Osteo arthritis knees
you have been called to see because of
high serum creatinine is 2000 µmol/l
urea 100
K 5.5
What is next?

25. Acute Kidney Injury Scenario 2
Vital Signs
Result
Normal Range
Pulse
98/min
60-100/min
Blood pressure
146/67 mmHg
130/80 mmHg
Temperature
37.5°C °C
Jugular venous pressure was normal ,
Cardiovascular examination:
Normal first and second heart sound no added sound or murmurs.
Respiratory system examination:
Lungs are clear to percussion and auscultation
Abdominal examination:
tenderness over supra pubic area, liver and spleen were not palpable.

26. Acute Kidney injury Scenario 2
Complete blood count (CBC)
Result
Normal reference ranges
Hemoglobin
146 g/L
Male : g/L ( g/dl )
Female : g/L ( g/dl )
White cell count
9 x 10* 9/L
x 10* 9/L
Platelet count
178 x 10*9/L
x 10* 9/L

27. Acute Kidney Injury Scenario 2
Test
Value
Normal values
Creatinine
2000 µmol/L
µmol/L
Urea
100 mmol/L
mmol/L
Potassium
5.5 mmol/L
mmol/L
Sodium
137 mmol/L
mmol/L
Bicarbonate 11
22-26 mmol/l

28. Acute Kidney Injury Result Normal values Color Dark Amber yellow
Character
clear PH
6.0 acidic
Specific gravity
1.021
Protein
(-)
Glucose
Red blood cells
11 /hpf
Hemoglobin
Negative
Pus cells (WBC)
1-2 /hpf
Epithelial cells
Amorphus phosphate
Bacteria
Granular cast

29. Acute Kidney Injury Scenario 2

30. Acute Kidney Injury Scenario 2

31. Renal

32. Tubular injury Ischemia: Totoxic
Hypotension, sepsis, prolonged pre-renal state
Totoxic
Heme pigment (rhabdomyolysis, intravascular hemolysis)
Crystals (tumor lysis syndrome, seizures, ethylene glycol poisoning, megadose vitamin C, acyclovir, indinavir, methotrexate)
Drugs (aminoglycosides, lithium, amphotericin B, pentamidine, cisplatin, ifosfamide, radiocontrast agents)

33. Tubular injury

34. Cast formation

36. Acute Kidney Injury Scenario 3
25 years old Saudi male sustained Road traffic accident this morning in ER was hypotensive and required 6 units of blood transfusion urine out put decreased significantly serum creatinine 285µmol/l?
How would you approach this patient?
What other information you need to know?

37. Acute Kidney Injury Scenario 3
Previously healthy
And urine output for the last 3 hours is <10 cc and dark colour

38. Acute Kidney Injury Scenario 3
Vital Signs
Result
Normal Range
Pulse
134/min
60-100/min
Blood pressure
80/55 mmHg
130/80 mmHg
Temperature
37.0°C °C
Jugular venous pressure was low, cold periphery,
Cardiovascular examination:
Normal first and second heart sound no added sound or murmurs.
Respiratory system examination:
Lungs are clear to percussion and auscultation
Abdominal examination:
No tenderness, liver and spleen were not palpable.

39. Acute Kidney Injury Scenario 3
Test
Value
Normal values
Creatinine
350 µmol/L
µmol/L
Urea
29 mmol/L
mmol/L
Potassium
6.2 mmol/L
mmol/L
Sodium
137 mmol/L
mmol/L
Bicarbonate 16
22-26 mmol/l

40. Acute Kidney injury Scenario 3
Complete blood count (CBC)
Result
Normal reference ranges
Hemoglobin
70 g/L
Male : g/L ( g/dl )
Female : g/L ( g/dl )
White cell count
12 x 10* 9/L
x 10* 9/L
Platelet count
198 x 10*9/L
x 10* 9/L

41. Acute Kidney Injury Result Normal values Color Dark Amber yellow
Character
clear PH
6.0 acidic
Specific gravity
1.003
Protein +2
(-)
Glucose
Red blood cells
1-2 /hpf
Hemoglobin
Negative
Pus cells (WBC)
Epithelial cells
Amorphus phosphate
Bacteria
Granular cast
seen

42. Acute Kidney Injury Scenario 3
What is your diagnosis?
Acute Kidney Injury
Where is the etiology?
Renal?
ATN (acute tubular necrosis)
AIN (acute interstitial nephritis)
GN (glomerulonephritis)
Diagnosis:
Acute Kidney Injury secondary to Acute tubular necrosis due to shock

43. Acute Kidney Injury Acute Tubular Necrosis (ATN)
Ischemia:
Hypotension, sepsis, prolonged pre-renal state
Totoxic
Heme pigment (rhabdomyolysis, intravascular hemolysis)
Crystals (tumor lysis syndrome, seizures, ethylene glycol poisoning, megadose vitamin C, acyclovir, indinavir, methotrexate)
Drugs (aminoglycosides, lithium, amphotericin B, pentamidine, cisplatin, ifosfamide, radiocontrast agents)
Diagnose by history,  FENa (>2%)
sediment with coarse granular casts,
Treatment is supportive care:
Maintenance of euvolemia (with diuretics, IVF, as necessary)
Avoidance of hypotension
Avoidance of nephrotoxic medications (including NSAIDs and ACE-I)
Dialysis, if necessary
80% will recover, if initial insult can be reversed

44. Acute Kidney Injury Pre renal vs ATN
Acute Tubular necrosis (ATN)
Urea/ Creatinine ration
>20:1
10-15:1
Urine
Normal
Muddy brown casts
Urine Osmolality
> 500
<350
Urine Na
<20
>20
Fractional excretion of Na
<1 %
> 1%
                    UNa   x   PCr   FENa   =   —————  x  100                    PNa   x   UCr
FENa < 1% (Pre-renal state)
Contrast nephropathy
Acute GN
Myoglobin induced ATN
FENa > 1% (intrinsic cause of AKI)

45. Acute Kidney Injury Scenario 3
Indication for dialysis in acute kidney injury setting:
Symptoms of uremia ( encephalopathy,…)
Uremic pericarditis
Refractory volume over load
Refractory hyperkalemia
Refractory metabolic acidosis

46. Interstitial

47. Interstitial

48. Interstitial

49. Acute Kidney Injury Scenario 4
56 years old male
known to have:
Bronchial asthma
Developed fever, sore throat and cough, Seen by his family doctor who prescribed him Amoxicillin tabs 24 hours later he started to have itching and skin rash , sough medical advice found to have high creatinine

50. Acute Kidney Injury Scenario 4
Vital Signs
Result
Normal Range
Pulse
95/min
60-100/min
Blood pressure
123/67 mmHg
130/80 mmHg
Temperature
37.0°C °C
Jugular venous pressure was normal , maculopapular rash all over the body
Cardiovascular examination:
Normal first and second heart sound no added sound or murmurs.
Respiratory system examination:
Lungs are clear to percussion and auscultation
Abdominal examination:
No tenderness, liver and spleen were not palpable.

51. Acute Kidney injury Scenario 4
Complete blood count (CBC)
Result
Normal reference ranges
Hemoglobin
146 g/L
Male : g/L ( g/dl )
Female : g/L ( g/dl )
White cell count
13 x 10* 9/L
esinophilia
x 10* 9/L
Platelet count
198 x 10*9/L
x 10* 9/L

52. Acute Kidney Injury Scenario 4
Test
Value
Normal values
Creatinine
123 µmol/L
µmol/L
Urea
10 mmol/L
mmol/L
Potassium
4.3 mmol/L
mmol/L
Sodium
137 mmol/L
mmol/L
Bicarbonate 22
22-26 mmol/l

53. Acute Kidney Injury Result Normal values Color Dark yellow
Amber yellow
Character
clear PH
6.0 acidic
Specific gravity
1.025
Protein +1
(-)
Glucose
Red blood cells
1-2 /hpf
Hemoglobin
Negative
Pus cells (WBC)
30-40 /hpf
Epithelial cells
Amorphus phosphate
Bacteria
Granular cast
WBC cast

54. Acute Kidney Injury Scenario 4

55. Acute Kidney Injury Scenario 4
What is your diagnosis?
Acute Kidney Injury secondary to interstitial nephritis
What is the treatment of this condition?
D/C Amoxicillin

56. Glomerular  
Anti–glomerular basement membrane (GBM) disease (Goodpasture syndrome)
Anti–neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-associated GN) (Wegener granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis)
Immune complex GN (lupus, postinfectious, cryoglobulinemia, primary membranoproliferative glomerulonephritis)

57. Glomerular

58. Acute Glomerulonephritis
Rare in the hospitalized patient
Diagnose by history, hematuria, RBC casts, proteinuria (usually non-nephrotic range), low serum complement in post-infectious GN), RPGN often associated with anti-GBM or ANCA
Usually will need to perform renal biopsy

59. Clinical feature-1 Signs and symptoms resulting of primary disease
Signs and symptoms resulting from loss of kidney function:
decreased or no urine output, flank pain, edema, hypertension, or discolored urine
weakness and
easy fatiguability (from anemia),
anorexia,
vomiting, mental status changes or
Seizures
edema

60. Clinical feature-2 Asymptomatic elevations in the plasma creatinine
abnormalities on urinalysis
Systemic symptoms and findings:
fever
arthralgias,
pulmonary lesions

61. AKI Diagnosis Blood urea nitrogen and serum creatinine
CBC, peripheral smear, and serology
Urinalysis
Urine electrolytes
U/S kidneys
Serology: ANA,ANCA, Anti DNA, HBV, HCV, Anti GBM, cryoglobulin, CK, urinary Myoglobulin

62. AKI Diagnosis Urinalysis Unremarkable in pre and post renal causes
Differentiates ATN vs. AIN. vs. AGN
Muddy brown casts in ATN
WBC casts in AIN
RBC casts in AGN
Hansel stain for Eosinophils

63. Contrast nephropathy 12-24 hours post exposure, peaks in 3-5 days
Non-oliguric, FE Na <1% !!
RX/Prevention:
1/2 NS 1 cc/kg/hr 12 hours pre/post
N-acetyle cystein 600 BID pre/post (4 doses)
Risk Factors:
CKD,
Older age
Hypovolemia ,DM,CHF

64. Rhabdomyolysis
Diagnose with  serum CK (usu. > 10,000), urine dipstick (+) for blood, without RBCs on microscopy, pigmented granular casts
Common after trauma (“crush injuries”), seizures, burns, limb ischemia occasionally after IABP or cardiopulmonary bypass
Treatment is largely supportive care. With IVF

65. Atheroembolic ARF
Associated with emboli of fragments of atherosclerotic plaque from aorta and other large arteries
Diagnose by history, physical findings (evidence of other embolic phenomena--CVA, ischemic digits, “blue toe” syndrome, etc), low serum C3 and C4, peripheral eosinophilia, eosinophiluria, rarely WBC casts
Commonly occur after intravascular procedures or cannulation (cardiac cath, CABG, AAA repair, etc.)

66. Acute Kidney Injury Summary
Acute kidney injury is a syndrome characterised by the rapid loss of the kidney's excretory function
Acute kidney injury is common and serious health problem which carry high mortality and morbidity
Acute kidney injury is amenable to prevention, early detection and treatment